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Genetic and methyla...
Genetic and methylation variation in the CYP2B6 gene is related to circulating p,p '-dde levels in a population-based sample
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- Lind, Lars (author)
- Uppsala universitet,Kardiovaskulär epidemiologi
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- Ng, Esther (author)
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
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- Ingelsson, Erik (author)
- Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA
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- Lindgren, Cecilia (author)
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Broad Institute of the Massachusetts Institute of Technology, Cambridge, USA; Broad Institute of Harvard University, Cambridge, USA,Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, USA
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- Salihovic, Samira, 1985- (author)
- Uppsala universitet,Örebro universitet,Institutionen för naturvetenskap och teknik,Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden,MTM Research Centre,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab
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- van Bavel, Bert, 1963- (author)
- Örebro universitet,Institutionen för naturvetenskap och teknik,MTM Research Centre, School of Science and Technology, Örebro University, Sweden
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- Mahajan, Anubha (author)
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
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- Lampa, Erik (author)
- Uppsala universitet,Kardiovaskulär epidemiologi
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- Morris, Andrew P. (author)
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK; Department of Biostatistics, University of Liverpool, Liverpool, UK
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- Lind, P. Monica (author)
- Uppsala universitet,Arbets- och miljömedicin
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(creator_code:org_t)
- Oxford, United Kingdom : Elsevier, 2017
- 2017
- English.
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In: Environment International. - Oxford, United Kingdom : Elsevier. - 0160-4120 .- 1873-6750. ; 98, s. 212-218
- Related links:
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https://doi.org/10.1...
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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Abstract
Subject headings
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- Objectives: Since the metabolism of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) is not fully known in humans, we evaluated if circulating levels of a major breakdown product of DDT, p,p'-DDE, were related to genome-wide genetic and methylation variation in a population-based sample.Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), circulating levels of p, p'-DDE were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS). Genetic variants were genotyped and imputed (1000 Genomes reference, March 2012 release). Methylation sites were assayed using the Illumina HumanMethylation450 array in whole blood. A genome-wide association study (GWAS) approach was applied.Results: Evidence for genome-wide significant association with p,p'-DDE levels was observed only for a locus at chromosome 19 corresponding to the CYP2B6 gene (lead SNP rs7260538). Subjects being homozygote for the G allele showed a median level of 472 ng/g lipid, while the corresponding level for those being homozygote for the T allelewas 192 ng/g lipid (p= 1.5x10(-31)). An analysis conditioned on the lead SNP disclosed a distinct signal in the same gene (rs7255374, position chr19: 41520351; p= 2.2 x 10(-8)). A whole-genome methylation analysis showed one significant relationship vs. p,p'-DDE levels (p= 6.2 x 10(-9)) located 7 kb downstreamthe CYP2B6 gene (cg27089200, position chr19: 41531976). This CpG-sitewas also related to the lead SNP (p = 3.8 x 10(-35)), but mediated only 4% of the effect of the lead SNP on p, p'-DDE levels.Conclusion: Circulating levels of p, p'-DDE were related to genetic variation in the CYP2B6 gene in the general elderly population. DNA methylation in this gene is not closely linked to the p, p'-DDE levels.
Subject headings
- NATURVETENSKAP -- Geovetenskap och miljövetenskap -- Miljövetenskap (hsv//swe)
- NATURAL SCIENCES -- Earth and Related Environmental Sciences -- Environmental Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Arbetsmedicin och miljömedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Occupational Health and Environmental Health (hsv//eng)
Keyword
- GWAS
- CYP2B6
- DDE
- Metabolism
- Methylation
- Enviromental Science
- Miljövetenskap
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Lind, Lars
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Ng, Esther
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Ingelsson, Erik
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Lindgren, Cecili ...
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Salihovic, Samir ...
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van Bavel, Bert, ...
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Mahajan, Anubha
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Lampa, Erik
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Morris, Andrew P ...
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Lind, P. Monica
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Earth and Relate ...
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and Environmental Sc ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Health Sciences
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and Occupational Hea ...
- Articles in the publication
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Environment Inte ...
- By the university
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Örebro University
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Uppsala University